1. Field of the Invention
This invention relates to the relief of pain, in particular to the control of pain by the topical application of a composition comprising a combination of remedies and certain adjuvants to enhance their effectiveness and assist transport of such remedies through a person's skin.
2. Prior Art
According to one of its aspects, this invention relates to the relief of pain. More particularly, this invention relates to the relief of pain generally deemed (by others than the sufferer) mild to moderate, such as headache, muscle ache, menstrual cramps, low back pain, arthralgia and the like for relief of which the so-called minor analgesics such as aspirin, acetaminophen, and ibuprofen are conventionally recommended. These minor analgesics are believed to have helped many people and are consumed in large quantities worldwide. They are, however, not free of unpleasant and even dangerous side effects, and new and improved remedies are constantly being sought.
This invention also relates to the relief of acknowledged severe pain for which controlled substance analgesics or narcotics are commonly offered. The concomitant dangers and drawbacks are well known and need no elaboration.
According to a further aspect, this invention relates to the relief of pain in one or more of a person's joints. More particularly, this invention relates to the relief of pain associated with those musculosketal disorders that primarily affect the joints. Joint disorders are further classified into the periarticular tissue disorders (eg tennis elbow) and the true articular or joint diseases (eg osteoarthritis). The MERCK MANUAL, 16th edition, published 1992, at pages 1297 to 1300, which portion is here incorporated by reference, contains a table titled "Classification of the Rheumatic Diseases" that includes ten major categories of disease including among others Diffuse Connective Tissue Diseases embracing rheumatoid arthritis and 17 other diseases and conditions; Arthritis associated with Spondylitis embracing 5 diseases and conditions; two kinds of Osteoarthritis; and 13 kinds of Arthritis, Tenosynovitis, and Bursitis associated with infectious agents. Most of these diseases and conditions are accompanied by pain. As pointed out by this publication, "we do not yet fully understand the causes of nor can we completely control joint pain."
Also according to this reference, a few types of arthritis are treatable with specific therapy; for example, gout can be completely controlled with drugs, or Lyme disease can be treated with antibiotics, but there are no "magic bullets" for most chronic rheumatic disorders. Optimal management for patients with severe musculosketeal disease requires many skills and resources and the collaboration of rheumatologists, orthopedic surgeons, paramedical specialists, and support services. Drug therapy is synergistic to other treatment in providing symptomatic control and suppression of disease and rarely should be relied alone. Disease suppression can be achieved with hypouricemic drugs for gout, corticosteroids and immunosuppressive agents for immunologic and inflammatory diseases, and a range of miscellaneous slow-acting drugs for rheumatoid arthritis and the arthropathies associated with spondylitis. Aspirin has been used for pain and inflammation since early in this century. More recent drug therapy for rheumatoid arthritis includes gold injections, penicillamine, hydroxychloroquine, and sulfasalazine. However, drug control of these conditions remains imperfect, and better understanding and new approaches are urgently needed.
For rheumatoid arthritis in particular, the same reference notes that among nonsteroidal anti-inflammatory drugs (NSAIDs), salicylates are relatively safe, inexpensive, analgesic, and anti-inflammatory, and are the traditional cornerstone of drug therapy in rheumatoid arthritis. Aspirin is begun with 600 to 1000 milligrams four times daily and adjusted upward until achieving a maximally effective or mildly toxic dose (eg tinnitus, diminished hearing) to a final dose from 3000 to 6500 milligrams per day. Other NSAIDs are available for patients who do not tolerate suficient aspirin to obtain a good effect, as shown in the following table:
______________________________________ Agent Recommended dosage ______________________________________ Indomethacin 25 milligrms three or four times daily Ibuprofen 400-800 mg four times daily Naproxen 250 mg twice daily or up to 1250 mg/day Fenoprofen 300-600 mg four times daily, 3200 mg maximum Tolmetin 400 mg three times daily, 2000 mg maximum Sulindac 150-200 mg twice daily Meclofenamate 200-400 mg/day Ketoprofen 150-300 mg/day Proxicam 20 mg once daily Flurbiprofen 100 mg twice or three times daily Diclofenac 75 mg twice daily or 50 mg four times daily ______________________________________
While less irritating to the gastrointestinal tract than aspirin,these NSAIDs can also produce gastric symptoms and bleeding.
Gold and the other slowly acting drugs are considered for use when aspirin or other NSAIDs are not sufficiently beneficial after 3 to 4 months of treatment. These drugs, too, are unfortunately subject to toxic side effects.
Corticosteroids are the most dramatically effective short-term anti-inflammatory drugs, but rheumatoid arthritis is usually active for years, and clinical benefit from corticosteroids often diminishes with time.
Thus, there clearly exists a need for ways to control pain that are both more safe and more effective.
Mizushima et al U.S. Pat. No. 4,340,594 discloses a fat emulsion for parenteral or oral administration, having anti-inflammatory activity, comprising an anti-inflammatory steroid, soybean oil, a phospholipid, and water. The fat emulsion is useful in the therapeutic or prophylactic treatment of rheumatism, immulogical hemolytic anemia, idiopathic thrombacytopenic purpura and Paget disease, or in conjunction with kidney transplantation. The fat emulsion may be compounded, as stabilizer, with a high molelcular substance selected from albumin, dextran, vinyl polymers, nonionic surface active agents, gelatin, and hydroxyethylstarch. Polyoxyethylenepolyoxypropylene copolymer having average molecular weight 1000 to 20000 is disclosed as one kind of nonionic surfactant. There is no disclosure of any topical composition or administration of any agent through the skin.
Fawzi et al U.S. Pat. No. 4,783,450 discloses that lecithin enhances the penetration of a drug through the skin as well as a pharmaceutical composition adapted for transdermal administration comprising an active ingredient and an effective amount of lecithin. An active ingredient is defined as "an effective amount of any therapeutically active drug". The "preferred drugs" recited by categories and specific compounds include analgesics without any details.
Rasor et al U.S. Pat. No. 5,141,738 discloses an injectable contrast medium for use as an ultrasonic diagnostic agent, particularly for imaging the left side of the heart, comprising a liquid vehicle containing suspended therein (a) microparticles comprising a mixture of (i)a lipophilic surfactant and (ii) a non-surfactant water soluble solid inorganic salt, organic salt, or solid hydroxy compound, and (b) microbubbles to render the mediim ultrasonic image enhancing. A homeopathic trituration of galactose and magnesium stearate is disclosed as one such inorganic solid. However, conventional surfactants which have an HLB value above about 20, e.g. sodium lauryl sulfate, sodium dodecylbenzenesulfonate and the commercially available nonionic surfactants, e.g. the Pluronics, do not enhance practical left heart contrast; their use in conjunction with ultrasonic contrast agents intended for left heart imaging would appear to be contraindicated. There is no mention of transdermal administration of anything.
Mantelle U.S. Pat. No. 5,332,576 discloses a composition for topical application substantially free of water and substantially water insoluble comprising (a) a therapeutically effective amount of at least one local anesthetic, (b) a pharmaceutically acceptable solvent, and (c) a flexible, finite, polysaccharide bioadhesive carrier. The solvent is preferably a polyhydric alcohol or combination of polyhydric alcohols, ie any organic polyalcohol including dipropylene glycol, propylene glycol, polyethylene glycol, glycerin, butylene glycol, hexylene glycol, polyoxyethylene, polypropylene glycol, sorbitol, ethylene glycol, and the like. Lecithin can be included as a binder. Pharmaceutically active agents in the composition can include any of 48 categories and the individual members thereof disclosed at column 18 line 37 to column 21 line 23.
Crandall U.S. Pat. No. 5,639,740 discloses methods and compositions for topically treating keratinous structures of humans and animals including skin, hair, fingernails, toenails, hooves, and horns by topically applying a composition comprising lecithin, isopropyl palmitate and water, which composition is called lecithin organogel. Lecithin organogel is optionally included in combination with an approximately 20% solution of PLURONIC F-127 (BASF, Parsippany N.J.) otherwise known as poloxamer 407 in a ratio of approximately 1:4. Crandall's composition can include pharmaceutically acceptable components such as gelling agents, compounding agents, and scents, and other pharmaceutically active agents such as antibacterial, antifungal, antiprotozoal or antiviral agents. There is, however, no mention of any analgesic or anesthetic remedy or of treating pain or any condition not relating to keratinous structures.